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Andrew Rebeyka

Contents 1 C-JUN 1.1 Introduction 1.2 Psychological Influences 1.3 References

C-JUN

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Introduction

The c-Jun protein is a member of transcription factors which consist of a basic region leucine zipper region ^[1]. Originally identified by its homology to v-jun, the oncogene from the avian sarcomoa virus ^[2] Bossy-Wetzel, E., Bakiri, L., Yaniv, M. (1997). Induction of apoptosis by the transcription factor c-Jun. EMO Journal. Vol.16;7. 1695-1709 </ref>. All these leucine zipper factors bind to DNA in one of two states: homo or heterodimers ^[3]. In conjunction with the c-Fos protein these two proteins bind to specific regions of DNA strands. Together these two proteins form the c-fos/c-jun complex which help regulate cell growth and differentiation ^[1]. As can be been in the figure XXXXX, the strand becomes an elongated coiled coil. This is formed by residues at the a and d positions in each of the two monomers, whereby they create hydrophobic centers which conform to the "knobs into holes" model by Crick. ^[4]. amino acids at these a and d positions are each surrounded by 4 additional residues from adjacent a-helix monomer ^[4].

the a and d residues each exhibit varying types of packing in terms of this "knobs into holes" theory. According to Harbury et al.(24) the leucines at the a positions are packed "parallel" in such a way that the C-alpha-C-beta bond vector lies in a parallel manner to the C-alpha-C-alpha vector at the base of the acceptor hole on adjacent helix ^[1]. To date two seperate sites of phosphorylation have been identified. at the N-terminal end are the amino acids Ser63 and Ser73, which are phosphorylated in response to ras expression. When ras is expressed, and Ser63 and Ser73 are phosphorylated, transcriptional activity of c-Jun increases. the second site is located at the C-terminal which is very close in proximity to the DNA binding domain. Here the residues are Thr214, Ser226, and Ser 232 ^[5]. Unlike the two serines at the N-terminal end, phosphorylation at the C-terminal end inhibits DNA binding to c-Jun ^[5]. therefore with the expression of such oncogenes as ras lead to dephsphorylation of these three residues.

Psychological Influences

The stress-induced signalling cascade may also active c-Jun by phosphorylation. the N-ternminal protein kinase phosphorylates Ser63 and Ser73 ^[6] PMID:10064599 </ref> . Another mechanism for the activation however is interestingly through intracellular calcium concentrations. increasing these concentrations by opening the L-type voltage gated calcium channels It was found that the N-terminus contains both calcium and stress-regulated transcriptional activation domains ^[6]. According to the study,distinct mechanisms of c-Jun control function by calcium and stress signals ^[6].

References

1. ↑ ^{1.0 1.1 1.2} Junius FK, O'Donoghue SI, Nilges M, Weiss AS, King GF. High resolution NMR solution structure of the leucine zipper domain of the c-Jun homodimer. J Biol Chem. 1996 Jun 7;271(23):13663-7. PMID:8662824
2. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named four
3. ↑ Junius FK, O'Donoghue SI, Nilges M, Weiss AS, King GF. High resolution NMR solution structure of the leucine zipper domain of the c-Jun homodimer. J Biol Chem. 1996 Jun 7;271(23):13663-7. PMID:8662824
4. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named ref2
5. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named ref6
6. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named ref5